CAR-T Cells Combined With Dasatinib for Patients With Relapsed and/or Refractory B-cell Hematological Malignancies

Early Phase 1

Recruiting

• Conditions: Acute Lymphoblastic Leukemia, in Relapse; Acute Lymphocytic Leukaemia Refractory; Multiple Myeloma in Relapse; Non-Hodgkin's Lymphoma, Relapsed; Multiple Myeloma, Refractory; Non-Hodgkin's Lymphoma Refractory
• Interventions: Drug: CD19/BCMA Targeted CAR T-cells and dasatinib; Drug: CD19/BCMA Targeted CAR T-cells

• Registration Number: NCT04603872
• Lead Sponsor: Zhejiang University

Brief Summary

A Study of CD19/BCMA-targeted CAR-T Cells Combined With Dasatinib for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia, B-cell Non-Hodgkin's Lymphoma and Multiple Myeloma.

Detailed Description

This is a double-arm, single-center study. This study is indicated for relapsed and/or refractory B-cell acute lymphoblastic leukemia, B-cell non-Hodgkin's lymphoma and multiple myeloma, the selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 120 patients will be enrolled for this trial. Primary objective is to explore the safety.

Study Timeline

• Status Verified: 2020-10
• Study First Submitted: 2020-10-21
• Study First Submitted QC: 2020-10-21
• Study First Posted: 2020-10-27
• Last Update Submitted: 2020-10-27
• Last Update Posted: 2020-10-28
• Study Start: 2020-11-01
• Primary Completion: 2023-11-01
• Study Completion: 2026-11-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Histologically confirmed diagnosis of CD19+ ALL, CD19+ NHL, or BCMA+ MM per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines (2020.v2);

2. Relapsed or refractory B cell hematological malignancies (meeting one of the following conditions):

   1. CR not achieved after standardized chemotherapy;
   2. CR achieved following the first induction, but CR duration is less than 12 months;
   3. Ineffectively after first or multiple remedial treatments;
   4. 2 or more relapses;
   5. Relapse after hematopoietic stem cell transplantation;
   6. Extramedullary leisions which were ineffective to radiotherapy or chemotherapy;

3. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol/L;

4. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;

5. No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;

6. Estimated survival time ≥ 12 weeks;

7. ECOG performance status 0 to 2;

8. Women of childbearing age had negative pregnancy test during screening period and before administration, and agreed to take effective contraceptive measures at least one year after infusion.

9. Patients volunteer to participate in the study and sign the informed consent.

Exclusion Criteria

Subjects with any of the following exclusion criteria were not eligible for this trial:

1. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;
2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
3. Pregnant (or lactating) women;
4. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
5. Active infection of hepatitis B virus or hepatitis C virus;
6. Concurrent therapy with systemic steroids within 2 weeks prior toscreening, except for the patients recently or currently receiving in haledsteroids;
7. Previously treated with any CAR-T cell product or other genetically-modified T cell therapies;
8. Creatinine >2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin >2.0 mg/dl;
9. Other uncontrolled diseases that were not suitable for this trial;
10. Patients with HIV infection;
11. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Administration of CD19/BCMA Targeted CAR T-cells and dasatinib	CD19/BCMA Targeted CAR T-cells and dasatinib	Dose levels of CAR-T cells are based on clinical trials of similar foreign products. Meanwhile, dasatinib would be combined as the following regimens: 1) Dasatinib preconditioning CAR-T cells during the manufacturing; 2) Dasatinib for the intervention of cytokine release storm after CAR-T cell infusion; 3) Dasatinib for the intervention of neurotoxicities after CAR-T cell infusion; 4) Dasatinib for the phase of CAR-T cell decreasing.
Administration of CD19/BCMA Targeted CAR T-cells	CD19/BCMA Targeted CAR T-cells	Dose levels of CAR-T cells are based on clinical trials of similar foreign products.

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity (DLT)	Baseline up to 28 days after CAR T-cells infusion	Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs)	Up to 2 years after CAR T-cells infusion	Incidence of treatment-emergent adverse events \[Safety and Tolerability\]

Secondary Outcome Measures

Name	Time	Method
Multiple myeloma (MM), Overall response rate (ORR)	At Day 28	Assessment of ORR at Day 28
B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR)	At Week 4, 12, and Month 6, 12, 18, 24	Assessment of ORR (ORR = CR + PR) per Lugano 2014 criteria
B-ALL, Event-free survival (EFS)	Up to 2 years after CAR-T cells infusion	From the first infusion of CAR-T cells to the occurrence of any event, including death, relapse orgene relapse, disease progression (any one occurs first), and the last visit
B-NHL, disease control rate (DCR)	At Week 12 and Month 6, 12, 18, 24	Assessment of DCR (DCR=CR+PR+SD) per Lugano 2014 criteria
Instrumental Activities of Daily Living (IADL) score	At Baseline, Month 1, 3, 6, 9 and 12	Assessment of Instrumental Activities of Daily Living (IADL) scale \[max score: 56, min score: 14, higher scores mean a worse outcome\] at Baseline, Month 1, 3, 6, 9 and 12
Hospital Anxiety and Depression Scale (HADS) score	At Baseline, Month 1, 3, 6, 9 and 12	Assessment using Hospital Anxiety and Depression Scale (HADS) \[max score: 42, min score: 0, higher scores mean a worse outcome\] at Baseline, Month 1, 3, 6, 9 and 12
B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR)	At Month 1, 3, 6, 12, 18 and 24	Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24
MM, Overall survival (OS)	At Month 6, 12, 24	Assessment of OS at Month 6, 12, 24
Quality of life	At Baseline, Month 1, 3, 6, 9 and 12	Assessment using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale \[For item1-28: max score: 112, min score: 28, higher scores mean a better outcome; for item 28-29: max score: 14, min score: 2, higher scores mean a worse outcome\] to measure Quality of life at Baseline, Month 1, 3, 6, 9 and 12
Activities of Daily Living (ADL) score	At Baseline, Month 1, 3, 6, 9 and 12	Assessment using Activities of Daily Living (ADL) scale (Barthel Index) \[max score: 100, min score: 0, higher scores mean a better outcome\] at Baseline, Month 1, 3, 6, 9 and 12
B-ALL, Overall survival (OS)	Up to 2 years after CAR-T cells infusion	From the first infusion of CAR-T cells to death or the last visit

Trial Locations

Locations (1)

The First Hospital of Zhejiang Medical Colleage Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China